It has been established that cell- and antibody-mediated immunity contribute to resistance against syphilitic and frambesial infections. Syphilitic and frambesial immune serum can confer complete protection on recipient hamsters. Treponemicidal activity in the pooled immune serum is relatively high. Immune serum and its immunoglobulin fractions, especially IgG2, also kills treponemes in vitro. Depletion of C3 abrogated the ability of immune serum to confer protection on normal hamsters against treponemal infection. T cells from syphilitic or frambesial immune hamsters can also confer protection on recipient hamsters challenged with the homologous strain. The mechanism by which T cells and antibody with complement confers protection on recipients against treponemal infection is not yet understood. Presumably macrophages are activated by T cells to kill treponemes using complement-dependent, antibody- mediated mechanisms. Considering the variety of mechanisms involved in treponemal evasion of host defenses, it will be necessary to combine antibody, its fractions, complement, T cells and their subpopulations with macrophages to obtain destruction of treponemes. The specific aims of this proposal are to determine: 1) Whether the T-cell subpopulations S11-/38+ or S11-/38- obtained from syphilitic immune hamsters can confer protection on irradiated recipients against treponemal challenge, 2) Whether interleukin 2 (IL-2) production is inhibited in syphilitic hamsters, 3) Whether macrophages specifically activated by T cells or their subsets (S11-/38+ or S11-/38-) can kill treponemes in vitro in the presence or absence of treponemal immune serum or its immunoglobulin fractions (IgG1 or IgG2), and 4) Whether treponemal antigen(s) isolated with immune IgG2 can induce protection in hamsters against treponemal challenge. The immunoglobulin fraction (IgG2) will be helpful in obtaining treponemal antigens that can not only immunize hamsters against treponemal infection, but possibly induce the T-cell subsets to activate macrophages and influence antibody- mediated phagocytosis. Investigation of the mechanism of resistance by which hamsters respond to treponemal infection may delineate the mechanism by which humans respond to syphilitic or frambesial infection and help develop an effective vaccine.